Metabolic and transcriptomic signatures of the acute psychological stress response in the mouse brain

The acute stress response triggers various physiological responses such as energy mobilization to meet metabolic demands. However, the underlying molecular changes in the brain remain largely obscure. Here, we use a brief water avoidance stress (WAS) to elicit an acute stress response in mice. By employing RNA-sequencing and metabolomics profiling, we investigate the acute stress-induced molecular changes in the mouse whole brain. Aberrant expression of 60 genes was detected in the brain tissues of WAS-exposed mice. Functional analyses showed that the aberrantly expressed genes were enriched in various processes such as superoxide metabolism. In our global metabolomic profiling, total 43 brain metabolites were significantly altered by acute WAS. Metabolic pathways upregulated from WAS-exposed brain tissues relative to control samples included lipolysis, eicosanoid biosynthesis, and endocannabinoid synthesis. Acute WAS also elevated levels of branched-chain amino acids, 5-aminovalerates, 4-hydroxy-nonenal-glutathione, as well as mannose, suggesting complex metabolic changes in the brain. The observed molecular events in the present study provide a valuable resource that can help us better understand how acute psychological stress impacts neural functions. Comparative gene expression profiling analysis of RNA-seq data for one hemisphere of the forebrain tissue of 1 h water avoidance stressed mouse and its control.

急性应激反应可触发多种生理反应，例如动员能量以满足代谢需求。然而，大脑内的潜在分子变化在很大程度上仍未明确。本研究利用短暂避水应激（brief water avoidance stress, WAS）在小鼠体内诱发急性应激反应。通过RNA测序（RNA-sequencing）与代谢组谱分析（metabolomics profiling），我们对小鼠全脑内急性应激诱导的分子变化进行了研究。在暴露于WAS的小鼠脑组织中，共检测到60个基因的表达异常。功能富集分析显示，这些异常表达的基因富集于超氧化物代谢等多种生物学过程。在全局代谢组谱分析中，急性WAS处理使小鼠大脑中共计43种代谢物发生显著改变。与对照组样本相比，WAS暴露小鼠脑组织中上调的代谢通路包括脂解、类二十烷酸生物合成以及内源性大麻素合成。急性WAS处理还升高了支链氨基酸、5-氨基戊酸、4-羟基壬烯醛-谷胱甘肽以及甘露糖的水平，提示小鼠大脑内发生了复杂的代谢变化。本研究中观测到的分子事件为我们深入理解急性心理应激如何影响神经功能提供了宝贵的研究资源。本数据集涵盖对1小时短暂避水应激处理小鼠及其对照小鼠的前脑单侧脑组织RNA测序数据所开展的比较基因表达谱分析。